Expert Critique

FROM THE ASCO Reading Room

Neil Majithia, MDResident PhysicianMayo ClinicRochester, MN

The latest edition of the NCCN guidelines for breast cancer management recommends hypofractionated whole breast radiation therapy for patients with early-stage breast cancer who have undergone breast-conserving surgery. This strategy, which provides a higher dose of radiation over a shorter treatment duration, was proven equally effective as traditional radiation schedules in the START A and B trials in terms of local recurrence and overall survival, with a reduced risk of toxicity. This approach has already gained widespread traction in the U.K. and should be adopted for patients who receive radiation therapy for this indication. An alternative to whole breast radiation therapy is accelerated partial breast irradiation, although data on this modality is preliminary and requires careful use of selection criteria.

Full Critique

Hypofractionation is now the preferred regimen for whole breast irradiation in the new National Comprehensive Cancer Network (NCCN) guideline for the management of invasive breast cancer.

The Canadian group randomized women with invasive breast cancer who had undergone breast-conserving surgery and whole breast irradiation at either the standard of 50.0 Gy in 25 fractions over 35 days or 42.5 Gy in 16 fractions over 22 days (hypofractionation group), without a boost. In START B, a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 40 Gy in 15 fractions over 3 weeks, and nearly 50% of the patients received a boost.

"The data fell in support of hypofractionation for a select group of women," said Kilian E. Salerno, MD, who reviewed the locoregional treatment updates contained in Version 1.2016 of the guideline at the 21st NCCN Annual Conference in Hollywood, Fla. (An article about the NCCN Breast Cancer Guideline update for systemic therapy is here.

Both studies demonstrated at least equivalent or better disease outcomes (local control), at least equivalent if not better cosmesis, and at least an equivalent or better side effect profile for the hypofractionation regimens compared with the standard regimens.

"I will also let everyone know that this [hypofractionation] is for whole breast radiation; it is not to be routinely used in the post-mastectomy setting and when you're treating regional nodes," said Salerno, Director of Breast and Soft Tissue/Melanoma Radiation Oncology at Roswell Park Cancer Institute in Buffalo, N.Y.

Two recent publications from the University of Michigan and MD Anderson Cancer Center support improved acute effects with hypofractionation. "There's really no excuses for why radiation oncologists are not adopting this treatment regimen," she said.

Accelerated partial breast irradiation (APBI) can be delivered via several methods. The NCCN guideline for appropriateness of APBI concurs with a consensus statement from the American Society for Radiation Oncology (ASTRO), which says that women suitable for APBI are typically those over age 60 with small unifocal breast cancer (not pure ductal carcinoma in situ) with no node involvement and negative margins after surgery. The ASTRO APBI consensus statement is currently being updated.

Omission of radiation is acceptable in selected women with a lower risk of recurrence, specifically those age 70 or older with small primary cancers that are ER/PR-positive with negative nodes and negative margins and who advance to endocrine therapy.

Post-Mastectomy Locoregional Recommendations

The guideline contains an update on recommendations for post-mastectomy radiation (PMRT). For patients with four or more positive lymph nodes, whole breast irradiation with or without a boost to the tumor bed is recommended following lumpectomy; radiation to the chest wall following comprehensive nodal radiation is recommended following mastectomy (category 1 recommendations).

For patients with one to three positive lymph nodes in either setting, following lumpectomy, the recommendation is for treatment to the whole breast with or without a boost, and to strongly consider regional nodal radiation. Similarly, for women following mastectomy, the guideline language is to strongly consider regional nodal radiation.

After Neoadjuvant Systemic Therapy

Following neoadjuvant systemic therapy, radiation therapy is recommended as per maximal stage of either clinical staging pre-systemic therapy or pathologic staging.

For patients who present with inoperable or locally advanced breast cancer, neoadjuvant systemic therapy and appropriate management of the breast is recommended, with an axillary lymph node dissection followed by comprehensive radiation to the appropriate target.

Treatment of Recurrence

Salerno noted that the circumstances of patients with recurrence vary considerably, so the optimal way to advance individual outcome is with a multidisciplinary approach.

Management of recurrence depends on the extent of disease and prior therapies received (lumpectomy or mastectomy, extent of prior axillary staging, systemic therapy, and radiation and its target).

Regional Nodal Irradiation

The need for regional nodal irradiation is influenced by the prior surgical resection and the extent of axillary staging (either sentinel node or axillary dissection).

In determining whether or not nodal irradiation is indicated for a particular patient, look not to a single study: "We need to think about all of the studies that are relevant," she said. "There are a number of them." Some studies were conducted in the setting of breast-conserving surgery whereas others were performed in the post-mastectomy setting. Some of the studies sought to answer surgical questions about management of the axilla rather than the appropriateness or regional nodal irradiation.

Study results obtained with regional node irradiation are applicable only if the presenting patient met the eligibility criteria for the study, she added. An individualized risk assessment for recurrence is paramount, and "there is no perfect way to do this."

Nomograms from Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center may be helpful but often produce disparate results: "And most importantly, you and your patient need to make a threshold at which point the risk is or is not worth treatment," Salerno said. "So there is no answer to using a nomogram in and of itself."

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